Oxygen benzyl ether

An isopropyl ether was developed as a phenol protective group that would be more stable to Lewis acids than would be an aryl benzyl ether. The isopropyl group has been tested for use in the protection of the phenolic oxygen of tyrosine during peptide synthesis."... 

You will note that the oxygen atoms attached to carbons 5 and 12 in 43 reside in proximity to the C-9 ketone carbonyl. Under sufficiently acidic conditions, it is conceivable that removal of the triethylsilyl protecting groups would be attended by a thermodynamically controlled spiroketalization reaction.30 Indeed, after hydro-genolysis of the C-26 benzyl ether in 43, subjection of the organic residue to the action of para-toluenesulfonic acid in a mixture of methylene chloride, ether, and water accomplishes the desired processes outlined above and provides monensin methyl ester. Finally, saponification of the methyl ester with aqueous sodium hydroxide in methanol furnishes the sodium salt of (+)-monensin [(+)-1], Still s elegant synthesis of monensin is now complete.13... 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

Pd/CaC03 is also used for the hydrogenolysis of benzyl-oxygen bonds.152 Hydrogenation and hydrogenolysis of an unsaturated benzyl ether over 5% Pt/ C and Pd(OH)2 gave the saturated and deprotected product.153 In contrast, transfer hydrogenolysis with 1,4-cylohexadiene or ammonium formate failed to provide the product cleanly, rapidly, or dependably. 

These results strongly suggest that in coal structure the covalent bond of benzyl ethers composed of aliphatic carbon and oxygen will be entirely cleaved at temperatures lower than 400°C, and the covalent bond composed of aromatic carbon and oxygen will be considerably decomposed at 450°C, since the unit structure of bituminous coal is considered to be composed of polynucleus of several benzene rings. 

In addtion to Sm metal, Cp 2Sm(TFlF)B (n = 2 or 0) can be a good starting material for allylsamarium generation. In the case of Cp 2Sm(THF) (n = 2 or 0), allylic ethers are useful precursors since they are able to coordinate to the low-valent lanthanide metal via the internal oxygen. Samarium complexes 45 react with allyl benzyl ether 46 to produce allylsamarium complex 47 and benzyloxide 48 as illustrated in Equation (9).26... 

The availability of oxepins that bear a side chain containing a Lewis basic oxygen atom (entry 2, Table 6.4) has further important implications in enantioselective synthesis. The derived alcohol, benzyl ether, or methoxyethoxymethyl (MEM) ethers, in which resident Lewis basic heteroatoms are less sterically hindered, readily undergo diastereoselective uncatalyzed alkylation reactions when treated with a variety of Grignard reagents [17]. The examples shown below (Scheme 6.7) demonstrate the excellent synthetic potential of these stereoselective alkylations. 

Oxygen-Substituted Benzylic Organometallic Compounds From Benzyl Ethers... 

Typical examples for type 2 are the cleavage of the carbon-oxygen bond in benzylic ethers (X = OR) either directly or indirectly via triarylamine cation radicals [49] (Eq. 22.42), the cleavage of the carbon-nitrogen bond in amines (X = NR2) [50] (Eq. 22.43), and the cleavage of the carbon-sulfur bond in sulfides (X = SR) [51] (Eq. 22.44) ... 

The hydrogenolysis of methyl 3,5-0-benzylidene-a- and -J3-D-xylofuranoside derivatives gave 5-benzyl ethers as main products. In some cases the attack of the reagent occurred at the ring oxygen of the furanoside skeleton to yield 5-O-benzyl-1 -O-methyl-xylitol derivatives [200]. 

Regioselective reductive openings of mixed phenolic-benzylic cyclic acetals, using BH3-NMe3-AlCl3, under mild conditions to yield a benzylic ether and free the phenol group have been attributed to association of boron with the more basic oxygen (benzylic) followed by reaction with aluminium chloride.309... 

The lithiation of a series of aryl benzyl ethers containing fluorine and methoxy groups has been studied.73 It has been found that the presence of one or two fluorine atoms in the meta -position relative to the oxygen atom prevents the lithiation at the benzyl carbon atom. 

Regioselective debenzylation can be achieved by treatment with Lewis acids such as ferric chloride and S11CI4 or under acetolysis conditions with acetic anhydride and sulfuric acid, and several examples are depicted in Scheme 2.3.9 Acetolysis results in cleavage of the most acid-sensitive benzyl group. In general, primary benzyl ethers can be selectively acetolysed in the presence of secondary benzyl ethers. The regioselectivity of the reaction can be explained as follows sulfuric acid protonates acetic anhydride followed by the formation of an acetyl ion and acetic acid. The acetyl ion reacts with the sterically most accessible oxygen which is at... 

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